There are two forms of hyperhomocysteinemia that result from disorders in distinct metabolic pathways: remethylation and transsulfuration. Defects in the remethylation result in hyperhomocysteinemia under fasting conditions, due primarily to deficiencies in folate and vitamin B12. Additional data indicate that riboflavin status may be an important determinant of fasting hyperhomocysteinemia as well. Defects in transsulfuration are associated with only mild elevations of homocysteine under fasting conditions but substantial elevations after a methionine load. Originally considered to be due to heterozygous cystathionine beta-synthase deficiency, recent data indicate that in a population-based setting, post-methionine load (PML) hyperhomocysteinemia results primarily from inadequate vitamin B6 status, although data from uncontrolled trials and observational studies suggest a possible involvement of the remethylation pathway and its associated nutrients in determination of the PML homocysteine increase. A large body of evidenced suggests that even mild to moderate elevations in fasting plasma homocysteine may cause an increased risk of occlusive vascular disease. More recent data suggest that PML hyperhomocysteinemia is also a potentially strong risk factor for vascular disease, which is independent of fasting hyperhomocysteinemia. It has been clearly demonstrated that elevated fasting homocysteine levels are amenable to treatment with higher levels of supplementation with folic acid and vitamin B12. The role of nutrition in modulating the function of the transsulfuration pathway, as assessed by the degree of PML increase in homocysteine concentration from baseline fasting concentrations, remains uncertain. The investigators have designed the current study to address these uncertainties. They plan to conduct a 12-week two-factor intervention in 180 males and female outpatients 35-75 years old with cardiovascular disease. Subjects will be given either a 30mg vitamin B6 supplement plus a placebo, a supplement containing 2mg of folic acid, 400 micrograms of vitamin B12, and 5mg of riboflavin plus a placebo, both active treatments, or neither treatment (i.e., double placebo) in a factorial design. The specific aims of this project are as follows: 1) to evaluate the effect of 12 weeks of supplementation with vitamin B6 on PML homocysteine increase from fasting levels in a population of patients with documented cardiovascular disease; 2) to evaluate the effect of 12 weeks of a supplementation with folic acid, vitamin B12, and riboflavin on PML homocysteine increase from fasting levels in a population of patients with documented cardiovascular disease.